The present invention relates to expandable, biodegradable stents. More particularly, the present invention relates to intravascular stents that have a programmed pattern of in vivo degradation and, thus, are useful for inhibiting the chronic restenosis that commonly occurs following percutaneous transluminal coronary angioplasty of atherosclerotic arteries.
Atherosclerosis is a disease in which vascular lesions or plaques consisting of cholesterol crystals, necrotic cells, lipid pools, excess fiber elements and calcium deposits accumulate on the interior walls of an individual's arteries. The presence of such plaques in the artery leads to thickening of the arterial wall and narrowing of the lumen. Eventually the enlargement of such plaques can lead to an occlusion of the lumen of the artery at the site of the lesion. One of the most successful procedures for treating atherosclerosis of the coronary arteries is percutaneous transluminal coronary angioplasty, hereinafter referred to as "PTC angioplasty". PTC angioplasty consists of introducing a deflated balloon into the lumen of the atherosclerotic artery, placing the balloon adjacent the site of the plaque or atherosclerotic lesion, inflating the balloon to a pressure of approximately 6 to 20 atmospheres thereby "cracking" the plaque and increasing the cross-sectional area of the lumen of the artery.
Unfortunately, the pressure that is exerted on the plaque during PTC angioplasty also traumatizes the artery. Accordingly, in 30-40% of the cases the vessel either gradually renarrows or recloses at the locus of the original stenotic lesion. This gradual renarrowing or reclosure, which is hereinafter referred to as "chronic restenosis," is a phenomenon that occurs almost exclusively during the first three to six months following angioplasty. Studies of the mechanism of chronic restenosis have shown that it is due in large part to a chronic constriction of the artery at the site of the barotraumatization, hereinafter referred to as the "retractile form of restenosis", and to a lesser extent to a proliferation of smooth muscle cells, hereinafter referred to as the "proliferative form of restenosis". Lafont et al. (1995) Restenosis After Experimental Angioplasty, Circulation Res. 76:996-1002.
A number of approaches for preventing restenosis are currently being used or tested. One approach involves the use of bioactive agents to prevent proliferation of the smooth muscle cells. To date, the use of bioactive agents alone has proven to be unsuccessful. Another approach employs a metallic stent which is deployed at the site of the stenotic lesion following PTC angioplasty. Typically, metallic stents are made in the form of a mesh-like network of linked wires and open spaces. Although metallic stents have the mechanical strength necessary to prevent the retractile form of restenosis, their presence in the artery can lead to biological problems including vasospasm, compliance mismatch, and even occlusion. Occasionally, technical difficulties, including distal migration and incomplete expansion, have also been observed with metallic stents. Moreover, there are inherent, significant risks from having a metal stent permanently implanted in the artery, including erosion of the vessel wall. In addition, the constant exposure of the stent to the blood can lead to thrombus formation within the blood vessel.
Metallic stents do not inhibit the proliferative form of restenosis. Indeed, implantation of the metallic stent induces neointimal proliferation. Such neointimal proliferation leads to the accumulation of new cells in the open spaces of the mesh-like metallic stents and on the inside surfaces thereof. This neointimal proliferation is one of the primary causes of the restenosis that occurs in the 30% of the patients who suffer from restenosis while the metallic stent is in place.
Finally, metallic stents prevent vascular remodeling. Vascular remodeling is a physiological process of the arterial wall that occurs as the atherosclerotic plaque begins to narrow the lumen of the vessel. When this occurs the artery senses the increased wall shear stress and tensile stress. In response to these stresses, the artery attempts to enlarge the lumen. Such enlargement is thought to be the result of expansion of the arterial wall through a process of cellular proliferation which results in increasing the luminal length (i.e. partial circumference) of the arterial wall. Glagou et al (1987) Compensatory Enlargement of Human Atheroscleotic Coronary Arteries, N. Eng. J. Med. 316:1371-1375. Although this process is not without limit, it can allow for relative reformation of a normal lumen cross-sectional area even with a 40% atherosclerotic stenosis of the arterial walls.
Stents made from biodegradable polymers have also been suggested for preventing restenosis. Although, generally an attractive alternative to metallic stents, testing in animals has shown that biodegradable stents still suffer from multiple complications, including distal migration of the entire stent or portions thereof and formation of an occlusive thrombus within the lumen of the stent. Frequently, such polymeric stents are formed from a mesh-like polymer which results in a stent having holes or open spaces that allow growth of tissue into and around the stent. As with the metallic stents, restenosis can result from the accumulation of proliferating smooth muscle cells on the inside surface of such polymeric stents.
Accordingly, it is desirable to have a new stent design that overcomes the disadvantages of the current stent designs. A stent that prevents retractile restenosis and that minimizes the restenosis that results from neointimal proliferation within a permanent stent is desirable. A stent that is fully degradable in vivo and that is designed such that portions of the stent are incorporated into the wall of the passageway, particularly an artery, during the time the stent is being degraded is desirable. A biodegradable stent that is designed to allow physiologic enlargement of the lumen of the blood vessel via expansive remodeling of the arterial wall during the first three to six months following PTC angioplasty is especially desirable.